Number Of CD4 CD25 Research Articles

Causal relationship between circulating immune cells and gastric cancer: a bidirectional Mendelian randomization analysis using UK Biobank and FinnGen datasets.

The role of immune cells in cancer pathogenesis remains controversial due to conflicting reports, potentially arising from various confounding factors. Emerging evidence suggests that cancer can also influence immune cell populations and functions, making it challenging to investigate their causal relationship. Traditional observational studies often fail to eliminate all confounding factors and are prone to reverse causality. Therefore, we employ Mendelian randomization (MR) to determine the causal relationship between immune cells and cancer, as this method can identify causal relationships independent of confounding factors and avoid reverse causality. Genome-wide association study (GWAS) summary statistics on immune traits, encompassing 310 immune cell phenotypes, were obtained from 3,757 European individuals, with peripheral blood immune cells tested using flow cytometry. GWAS summary statistics for gastric cancer were derived from 476,116 European individuals across two large-scale biobanks: the UK Biobank and FinnGen. Gastric cancer was identified by the International Classification of Diseases, 9th Revision (ICD-9), and 10th Revision (ICD-10) codes. Significant single nucleotide polymorphisms (SNPs) for immune traits were extracted at a threshold of P<1×10-5, while a threshold of P<5×10-8 was used for gastric cancer GWAS data. Linkage imbalance-based clumping was performed to obtain independent SNPs, and those with F<10 were excluded to mitigate weak instrument bias. Phenoscanner V2 was used to exclude SNPs directly associated with potential confounders or outcomes. Two-sample MR was conducted using five MR methods, with inverse-variance-weighted (IVW) as the primary analysis method. A false discovery rate (FDR) correction was used to reduce the likelihood of type 1 errors. In addition, we conducted MR-Egger intercept tests and Cochran's Q tests. The numbers of CD4-CD8- T cells and IgD-CD27- B cells were positively correlated with the development of gastric cancer, with odds ratios (ORs) of 1.15 [95% confidence interval (CI), 1.07-1.24; P<0.001; PFDR=0.041; IVW method] and 1.07 (95% CI, 1.03-1.11; P=0.001; PFDR=0.187; IVW method), respectively. However, the percentage of IgD+CD24- B cells in lymphocytes were negatively associated with the development of gastric cancer (OR =0.90; 95% CI, 0.84-0.96; P=0.002; PFDR=0.187; IVW method). MR analysis of the above three immune cell phenotypes showed no significant heterogeneity or horizontal pleiotropy. In the reverse MR analysis, gastric cancer was not causally associated with any of the immune cell phenotypes. Circulating CD4-CD8- T cells and IgD-CD27- B cells are positively correlated with the development of gastric cancer, while the percentage of IgD+CD24- B cells in lymphocytes are negatively correlated. These findings provide insight into the relationship between immune cells and gastric cancer pathogenesis and may serve as a basis for the development of immunotherapies for gastric cancer.

Effect of GnRH immunocastration on immune function in male rats.

The present study aimed to reveal the effects of immunocastration on the development of the immune system in rats. Seventy rats were randomly assigned into two groups: Control (n = 35) and immunized (n = 35). Twenty-day-old rats were immunized with gonadotropin-releasing hormone (GnRH) and booster immunization was administered every two weeks (three immunizations in total). From 20-day-old rats, we collected samples every two weeks, including five immunized rats and five control rats (seven collections in total). We collected blood samples, testicles, thymuses, and spleens. The results showed that GnRH immunization increased the GnRH antibody titers and reduced the testosterone concentration (both P < 0.05). Compared with the control group, the number of CD4+CD8- cells, CD4-CD8+ cells, and CD4+CD8+ cells increased (P < 0.05) whereas the number of CD4-CD8- cells and CD4+CD25+ cells reduced in the immunized group (P < 0.05) over time. GnRH immunization also increased the relative weights of thymus and spleen (P < 0.05), serum concentrations of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17 and Interferon-γ (IFN-γ) over time (P < 0.05), and changed the mRNA levels of IL-2, IL-4, IL-6. IL-10, IL-17, IFN-γ, CD4, D8, CD19 GnRH, and GnRH receptor (GnRH-R) in thymus and spleen. Thus, GnRH immunization enhanced the immune markers in thymus, spleen, and blood immune cytokines in rats.

Role of CD4 +CD25 + T Cells in Children With Idiopathic Thrombocytopenic Purpura

CD4CD25 T cells play an important role in the induction and maintenance of peripheral self-tolerance. These professional regulatory cells prevent the activation and proliferation of potentially autoreactive T cells that have escaped thymic deletion. To investigate the role of CD4CD25 regulatory T cells in children with idiopathic thrombocytopenic purpura (ITP) and correlate their levels with different disease stages, this study was conducted in 45 children (15 controls and 30 cases with ITP); 10 of these patients were in the acute phase (Group I), 10 in the remission phase (Group II), and the remaining 10 in the chronic phase (Group III). Studied groups were subjected to the following investigations: complete blood count, erythrocyte sedimentation rate, Coombs test, and flow cytometric analysis of CD4CD25 T lymphocyte count. There was a highly significant decrease in platelet count and CD4CD25 count in patients of the acute group when compared with remission, chronic, and control groups. There was a significant decrease in CD4CD25 count in the chronic group when compared with remission group. In addition, a significant decrease in CD4CD25 count was found in remission group when compared with the control group. Moreover, there was a positive correlation between CD4CD25 count and platelet count in all the groups; this correlation was significant in the acute group and insignificant in the remission and chronic groups. Decreased number of CD4CD25 T cells might be one of the mechanisms that cause immune regulation dysfunction in ITP and the count of CD4CD25 T cells is considered to be related to the severity of ITP, as these cells were significantly decreased in the active phase of the disease and increased in the patients at the complete remission phase. Therefore, count of CD4CD25 T cells might be a helpful diagnostic predictor of onset and improvement of ITP in children. Finally, it is suggested that these cells may have therapeutic implications that need further clarification.

CD28-mediated signaling in vivo prevents activation-induced apoptosis in the thymus and alters peripheral lymphocyte homeostasis.

Activation of T lymphocytes can result in a functional immune response, anergy or apoptosis. Functional T cell activation requires the interaction of the TCR with Ag presented by MHC molecules on APC concurrent with appropriate interactions between cell surface accessory molecules. Interestingly, the level of CD28 expression is regulated during T cell development as well as during T cell activation and proliferation, suggesting that CD28 could play a role in determining the outcome of activation of TCR during T cell ontogeny. We identify, herein, a novel function of murine CD28 in the regulation of activation-induced apoptosis in thymocytes. In vivo, or combined in vivo and in vitro treatment with mAbs to CD28 prevents apoptosis of CD4+CD8+ thymocytes induced by Abs to the TCR complex. Prolonged administration of anti-CD28 Abs increased the number of both CD4+CD8- and CD4-CD8+ T cells in the thymus, while the number of CD4+CD8+ T cells is relatively unchanged. Furthermore, this treatment leads to a dramatic enlargement of peripheral lymphoid organs characterized primarily by the expansion of B cells. The number of CD4+CD8- T cells in the spleen of anti-CD28-treated mice is also moderately increased, while the number of CD4-CD8+ cells is relatively unchanged.

T cell development in insulin-like growth factor-II transgenic mice.

Growth hormone and insulin-like growth factor-I (IGF-I) have been demonstrated to play a role in T and B cell development. We studied the effects of IGF-II on T cell development in two transgenic mouse lines that overexpress human IGF-II under the control of the H2Kb promoter. The thymuses of 1-wk-old mice of two transgenic lines (5'-35 and 5'-74) contained 36 and 68%, respectively, more thymocytes than controls. Between 1 and 4 wk of age, the overexpression of IGF-II also resulted in a 2 to 2.5 times stronger increase in thymic cellularity. As in control mice, the number of thymocytes declined after 4 wk of age, and at 15 wk it was no longer significantly different from controls. Flowcytometric analysis indicated that at 2 and 4 wk of age, the increased thymic cellularity was associated with an increased number of early (CD4- CD8- or CD4- CD8dim), intermediate (CD4+CD8+), and mature thymocytes (CD3++CD4+CD8- or CD3++CD4-CD8+). However, the increase in the number of CD4+CD8- thymocytes was larger than the increase in the number of CD4-CD8+ thymocytes. As a consequence, CD4+ T cells mainly contributed to the increase in the number of T cells in spleen. These T cells showed a mature phenotype since they expressed CD3 and were negative for heat-stable antigen, a marker for immature T cells. These data indicate that overexpression of IGF-II increases thymic cellularity and stimulates the generation of phenotypically normal T cells with a preference to CD4+ cells.

Studies on the thymus in Chagas' disease. II. Thymocyte subset fluctuations in Trypanosoma cruzi-infected mice: relationship to stress.

Changes in thymic T-cell subsets in mice acutely infected with Trypanosoma cruzi have been studied in both C3H/HeJ and C57BL/6 mice. The significant decrease in thymocyte number, observed in both mouse strains on day 14 post-infection correlated with a drastic decrease in CD4+CD8+ cell number, whereas the number of CD4-CD8-, CD4+CD8- and CD4-CD8+ cells remained essentially unchanged. The important increase in CD3hi cell frequency confirmed that resistant thymocytes during Chagas' disease development were mostly medullary thymocytes, whereas the thymic cortex was largely depleted, as previously observed on thymus sections. This involution of the thymus could have been due to the increase of circulating glucocorticoid levels observed after infection. However, similar cell modifications were found in infected adrenalectomized mice whose serum corticosterone levels were only slightly augmented. Thus, the thymic alterations appear not to be linked to stress responses, at least those dependent on high levels of circulating glucocorticoids.